Technetium-99m sestamibi and thallium imaging have similar accuracy when used for detection of coronary artery disease (CAD), but whether sestamibi provides accurate information regarding myocardial viability in patients with chronic CAD and left ventricular (LV) dysfunction has not been established. Fifty-four patients (49M, 5F, ages 36-79) with chronic CAD and LV dysfunction underwent stress-redistribution- reinjection thallium tomography and same-day rest-stress sestamibi imaging. Of the 111 reversible thallium defects, 40 (36%) were determined to be irreversible on the rest-stress sestamibi study, while only 3 of 63 (5%) irreversible thallium defects were classified to be reversible by sestamibi imaging. Hence, the concordance regarding reversibility of myocardial defects between thallium stress- redistribution-reinjection and same day rest-stress sestamibi studies was 75%. A subgroup of 33 patients also underwent positron emission tomography (PET) studies with F-18 fluorodeoxyglucose at rest following an oral glucose load. Similar to the overall group of 54 patients, there was concordance between thallium and sestamibi imaging regarding defect reversibility in 57 of 76 (75%) regions. In the remaining 19 (25%) discordant regions, all 19 appeared irreversible by sestamibi imaging but were reversible by thallium imaging and metabolically active by PET. We then explored methods to improve the sestamibi results. First, when the 19 discordant regions with irreversible sestamibi defects were further analyzed according to the severity of defects, 17 (89%) demonstrated only mild-to-moderate reduction in sestamibi activity (51 to 85% of normal activity) suggestive of predominantly viable myocardium. Second, when an additional 4-hour redistribution image was acquired in 18 patients after the injection of sestamibi at rest, 6 of 16 (38%) discordant irreversible regions on the rest-stress sestamibi study became reversible, thereby increasing the concordance between thallium and sestamibi studies to 82%. Thus, when the clinical question is one of myocardial viability rather than exercise-induced ischemia, thallium and sestamibi studies provide concordant information in most abnormal regions.